Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8480198 | Seminars in Cell & Developmental Biology | 2016 | 10 Pages |
Abstract
The ErbB signaling network instructs the execution of key cellular programs, such as cell survival, proliferation and motility, through the generation of robust signals of defined strength and duration. In contrast, unabated ErbB signaling disrupts tissue homeostasis and leads to cell transformation. Cells oppose the threat inherent in excessive ErbB activity through several mechanisms of negative feedback regulation. Inducible feedback inhibitors (IFIs) are expressed in the context of transcriptional responses triggered by ErbB signaling, thus being uniquely suited to regulate ErbB activity during the execution of complex cellular programs. This review focuses on MIG6, an IFI that restrains ErbB signaling by mediating ErbB kinase suppression and receptor down-regulation. We will review key issues in MIG6 function, regulation and tumor suppressor activity. Subsequently, the role for MIG6 loss in the pathogenesis of tumors driven by ErbB oncogenes as well as in the generation of cellular addiction to ErbB signaling will be discussed. We will conclude by analyzing feedback inhibition by MIG6 in the context of therapies directed against ErbB and non-ErbB oncogenes.
Keywords
TKIHspPTCGBMGPCRAP-1LPADnmtPDGFSOCSARFHGFEGFRRTKSMADFBJ osteosarcoma oncogeneEBRLRIG1ERRFI1MIG6TKDDNA methyl-transferaseRALTTGFβFOSEGFFGFDMBAJnkERKc-Jun N-terminal kinaseG-protein coupled receptorMAPKMIGlysophosphatidic acidIHCTransforming Growth Factor BetaEMTTyrosine kinase domainREDColorectal cancerNSCLCTumor suppressionsuppressor of cytokine signalingHepatocyte growth factorADP-ribosylation factorplatelet-derived growth factorfibroblast growth factorFoxOphosphatase and tensin homologCasitas B-lineage lymphomaUTR یا untranslated regions untranslated regionFeedback inhibitionTyrosine kinase inhibitorHeat shock proteinactivator protein 1mitogen-activated protein kinasePtennon-small cell lung carcinomaPapillary thyroid carcinomaCRCCblextracellular signal-regulated kinaseGlioblastoma multiformeReceptor Tyrosine KinaseEpidermal growth factor receptorErbB receptors
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Authors
Sergio Anastasi, Dante Lamberti, Stefano Alemà , Oreste Segatto,